Synthesis of Selenium-Substituted
Pyrroles and Pyrazol-3-ones

Orazio A. Attanasi; Lucia De Crescentini; Fabio Mantellini; Francesca Marini; Simona Nicolini; Silvia Sternativo; Marcello Tiecco

doi:10.1055/s-0029-1216630

LETTER

Synthesis of Selenium-Substituted Pyrroles and Pyrazol-3-ones

Orazio A. Attanasi*^a, Lucia De Crescentini*^a, Fabio Mantellini^a, Francesca Marini^b, Simona Nicolini^a, Silvia Sternativo^b, Marcello Tiecco*^b
^a Istituto di Chimica Organica, Università degli Studi di Urbino ‘Carlo Bo’, Via I Maggetti, 24, 61029 Urbino (PU), Italy
Fax: +39(0722)303441; e-Mail: orazio.attanasi@uniurb.it; e-Mail: lucia.decrescentini@uniurb.it;
^b Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università di Perugia, 06123 Perugia, Italy

Abstract

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Abstract

An approach to the synthesis of 4-(phenylseleno)pyrroles, 4-(phenylseleno)pyrazol-3-ones, and 4-(1,3-benzoselenazol-2-ylthio)pyrazol-3-ones is described. Their formation passes through hydrazonic intermediates obtained by the reaction between 1,2-diaza-1,3-butadienes and 1-(phenylseleno)ketones, phenylselenol, or 2-mercaptobenzoselenazole, respectively.

Key words

1,2-diaza-1,3-butadienes - Michael additions - selenium - pyrroles - pyrazoles

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References

References and Notes

<A NAME="RD39109ST-1A">1a</A> Sundberg RJ. In Comprehensive Heterocyclic Chemistry Vol. 4: Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984. p.314

<A NAME="RD39109ST-1B">1b</A> Gribble GW. In Comprehensive Heterocyclic Chemistry II Vol. 2: Katritzky AR. Rees CW. Scriven EFV. Pergamon-Elsevier Science; Amsterdam: 1996. Chap. 4.

<A NAME="RD39109ST-2">2</A> Lipshutz BH. Chem. Rev. 1986, 86: 795

<A NAME="RD39109ST-3">3</A> Progress in Heterocyclic Chemistry Vol. 15-20: Gribble GW. Joule JA. Elsevier; Oxford: 2003-2008.

<A NAME="RD39109ST-4">4</A> Elguero J. Goya P. Jagerovic N. Silva AMS. In Targets in Heterocyclic Systems - Chemistry and Properties Vol. 6: Attanasi OA. Spinelli D. Società Chimica Italiana; Rome: 2002. p.52

<A NAME="RD39109ST-5A">5a</A> Attanasi OA. Caglioti L. Org. Prep. Proced. Int. 1986, 18: 299

<A NAME="RD39109ST-5B">5b</A> Attanasi OA. Serra-Zanetti F. In Progress in Heterocyclic Chemistry Vol. 7: Suschitzky H. Scriven EFV. Pergamon; Oxford: 1995.

<A NAME="RD39109ST-5C">5c</A> Attanasi OA. Filippone P. Synlett 1997, 1128

<A NAME="RD39109ST-5D">5d</A> Attanasi OA. De Crescentini L. Favi G. Filippone P. Mantellini F. Santeusanio S. ARKIVOC 2002, (xi): 274

<A NAME="RD39109ST-6A">6a</A> Attanasi OA. De Crescentini L. Favi G. Filippone P. Mantellini F. Santeusanio S. J. Org. Chem. 2004, 69: 2687

<A NAME="RD39109ST-6B">6b</A> Attanasi OA. Favi G. Filippone P. Lillini S. Mantellini F. Spinelli D. Stenta M. Adv. Synth. Catal. 2007, 349: 207

<A NAME="RD39109ST-6C">6c</A> Schmidt A. Karapetyan V. Attanasi OA. Favi G. Görls H. Mantellini F. Langer P. Synlett 2007, 2965

<A NAME="RD39109ST-6D">6d</A> Karapetyan V. Mkrtchyan S. Schmidt A. Attanasi OA. Favi G. Mantellini F. Villinger A. Fischer C. Langer P. Adv. Synth. Catal. 2008, 350: 1331

<A NAME="RD39109ST-7A">7a</A> Attanasi OA. Filippone P. In Topics in Heterocyclic Systems Vol. 1: Attanasi OA. Spinelli D. Research Signpost; Trivandrum: 1996. p.157

<A NAME="RD39109ST-7B">7b</A> Forlani L. Attanasi OA. Boga C. De Crescentini L. Del Vecchio E. Favi G. Mantellini F. Tozzi S. Zanna N. Eur. J. Org. Chem. 2008, 4357

<A NAME="RD39109ST-7C">7c</A> Attanasi OA. Baccolini G. Boga C. De Crescentini L. Giorgi G. Mantellini F. Nicolini S. Eur. J. Org. Chem. 2008, 5965

<A NAME="RD39109ST-8A">8a</A> Tiecco M. Testaferri L. Bagnoli L. Marini F. Santi C. Temperini A. Scarponi C. Sternativo S. Terlizzi R. Tomassini C. ARKIVOC 2006, (vii): 186

<A NAME="RD39109ST-8B">8b</A> Tiecco M. Electrophilic Selenium, Selenocyclizations, In Topics in Current Chemistry. Organoselenium Chemistry: Modern Developments in Organic Synthesis Wirth T. Springer; Heidelberg: 2000. Chap. 2. p.7

<A NAME="RD39109ST-8C">8c</A> Tiecco M. Carlone A. Sternativo S. Marini F. Bartoli G. Melchiorre P. Angew. Chem. Int. Ed. 2007, 42: 6882

<A NAME="RD39109ST-8D">8d</A> Tiecco M. Testaferri L. Temperini A. Terlizzi R. Bagnoli L. Marini F. Santi C. Org. Biomol. Chem. 2007, 5: 3510

<A NAME="RD39109ST-8E">8e</A> Tiecco M. Testaferri L. Santi C. Tomassini C. Marini F. Bagnoli L. Temperini A. Angew. Chem. Int. Ed. 2003, 42: 3131

<A NAME="RD39109ST-8F">8f</A> Organoselenium Chemistry - A Practical Approach Back TG. Oxford University Press; New York: 2000.

<A NAME="RD39109ST-8G">8g</A> Wirth T. Angew. Chem. Int. Ed. 2000, 39: 3742

<A NAME="RD39109ST-8H">8h</A> Petragnani N. Stefani HA. Valduga CJ. Tetrahedron 2001, 57: 1411

<A NAME="RD39109ST-8I">8i</A> Special issue: Curr. Org. Chem. 2006, 10: 1891

<A NAME="RD39109ST-9A">9a</A> Mugesh G. du Mont W.-W. Sies H. Chem. Rev. 2001, 101: 2125

<A NAME="RD39109ST-9B">9b</A> Nogueira CW. Zeni G. Rocha JBT. Chem. Rev. 2004, 104: 6255

<A NAME="RD39109ST-9C">9c</A> Soriano-Garcia M. Curr. Med. Chem. 2004, 11: 1657

<A NAME="RD39109ST-9D">9d</A> Narajji C. Karvekar MD. Das AK. Indian. J. Pharm. Sci. 2007, 8: 344

<A NAME="RD39109ST-9E">9e</A> Naithani R. Mini-Rev. Med. Chem. 2008, 69: 344

<A NAME="RD39109ST-10A">10a</A> Hartke K. Wendebourg HH. Heterocycles 1988, 27: 639

<A NAME="RD39109ST-10B">10b</A> Hartke K. Wendebourg HH. Liebigs Ann. Chem. 1989, 415

<A NAME="RD39109ST-10C">10c</A> Bella M. Piancatelli G. Squarcia A. Trolli C. Tetrahedron Lett. 2001, 41: 3669

<A NAME="RD39109ST-11">11</A> Dudnik AS. Sromek AW. Rubina M. Kim JT. Kel’in AV. Gevorgyan V. J. Am. Chem. Soc. 2008, 130: 1440

Synthesis of the α-Seleno Ketones 2a,bCompound 2a Phenyl selenyl chloride (5.0 mmol) was added at r.t. to acetone (4 mL), and the solution was stirred for 30 min. The reaction mixture was poured into H₂O and extracted with CH₂Cl₂. The organic layer was dried over Na₂SO₄, filtered, and evaporated under vacuum. The crude product 2a (89% yield) was used without further purification.
Compound 2b The phenylselenyl sulfate was generated from (PhSe)₂ (1.7 mmol) and (NH₄)₂S₂O₈ (2.3 mmol) in MeCN (20 mL) at 80 ˚C. After 30 min the 1-phenylethanone (1.7 mmol) was added. The mixture was stirred overnight at the same temperature, then was poured into an aq solution of NaHCO₃ and extracted with CH₂Cl₂. The organic layer was dried over Na₂SO₄, filtered, and evaporated under vacuum. The residue was purified by flash chromatography (elution mixture: PE-CH₂Cl₂ = 85:15) to yield 2b in 40% yield.

<A NAME="RD39109ST-12B">12b</A> Spectral data of 2a and 2b are identical to those already described in the literature: Houllemare D. Ponthieux S. Outurquin F. Paulmier C. Synthesis 1997, 101

General Procedure for the Synthesis of β-(Phenylseleno)-hydrazones 3a,b To a magnetically stirred solution of 1,2-diaza-1,3-butadiene 1a as a mixture of E/Z isomers [¹8] (1.0 mmol) and 1-(phenyl-seleno)acetone [¹²] (2a) or 1-phenyl-2-(phenylseleno)-ethanone [¹²] (2b, 1.0 mmol) in THF (5 mL) at r.t., a catalytic amount (0.1 mmol) of NaH was added. The reaction mixture was magnetically stirred for 1.0-1.5 h until the disappearance of the starting 1. β-(Phenylseleno)hydrazones 3a,b were obtained by chromatography on SiO₂ column (elution mixtures: cyclohexane-EtOAc) and by subsequent crystallization from Et₂O-light PE (40-60). The reaction between 1b,c and 2a,b gave complicated mixtures.
Data for Ethyl 2-[ N-(Aminocarbonyl)ethanehydra-zonoyl]-2,5-dideoxy-3- Se -phenyl-3-selenopent-4-ulosonate (3a)
Yield 294.5 mg (74%) obtained as yellow solid; mp 148-152 ˚C. IR (Nujol): ν_max = 3420, 3291, 3195, 1765, 1720, 1690 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.08 (t, 3 H, J = 6.8 Hz), 1.85 (s, 3 H), 2.32 (s, 3 H), 3.44 (d, 1 H, J = 11.6 Hz), 3.97-4.02 (m, 2 H), 4.70 (d, 1 H, J = 11.6 Hz), 6.38 (s, 2 H), 7.38-7.47 (m, 5 H), 9.30 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.8 (q), 15.2 (q), 27.7 (q), 49.3 (d), 53.8 (d), 60.8 (t), 125.5 (s), 128.8 (d), 129.1 (d), 136.2 (d), 142.4 (s), 156.9 (s), 169.3 (s), 202.0 (s); during the MS analysis, we have observed only the signals of pyrrole 4a. Anal. Calcd for C₁₆H₂₁N₃O₄Se: C, 48.25; H, 5.31; N, 10.55. Found: C, 48.19; H, 5.39; N, 10.63.

General Procedure for the Synthesis of 4-(Phenylseleno)-pyrroles 4a-c and 2-Oxohydrazones 5a,b To a magnetically stirred solution of 1,2-diaza-1,3-butadienes 1a-c as a mixture of E/Z isomers [¹8] (2.0 mmol) and 1-(phenylseleno)acetone [¹²] (2a, 1.0 mmol) or 1-phenyl-2-(phenylseleno)ethanone [¹²] (2b, 1.0 mmol) in THF (5 mL) at r.t., a stoichiometric amount (1.0 mmol) of NaH was added. The reaction mixture was magnetically stirred for 6.0-8.0 h until the disappearance of the starting 1. 4-(Phenyl-seleno)pyrroles 4a-c and 2-oxohydrazones [¹4] 5a,b were separated by chromatography on SiO₂ column (elution mixtures: cyclohexane-EtOAc), and they were crystallized from Et₂O-light PE (40-60) or EtOAc-light PE (40-60), respectively.
Ethyl 1-[(Aminocarbonyl)amino]-2,5-dimethyl-4-(phenylseleno)-1 H -pyrrole-3-carboxylate (4a) Yield 266.5 mg (70%) obtained as light yellow solid; mp 182-184 ˚C. IR (Nujol): ν_max = 3518, 3374, 3193, 1727, 1704 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.04 (t, 3 H, J = 7.2 Hz), 2.10 (s, 3 H), 2.28 (s, 3 H), 4.03 (q, 2 H, J = 7.2 Hz), 6.38 (s, 2 H), 7.15-7.19 (m, 2 H), 7.49-7.53 (m, 2 H), 7.73-7.75 (m, 1 H), 9.29 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 10.8 (q), 13.9 (q), 14.2 (q), 58.8 (t), 98.5 (s), 110.3 (s), 118.7 (s), 125.3 (s), 128.2 (d), 128.8 (d), 134.2 (s), 145.9 (d), 156.9 (s), 164.3 (s). MS: m/z (%) = 383 (23) [M⁺ + 3], 381 (100) [M⁺ + 1], 379 (57) [M⁺ - 1], 378 (21) [M⁺ - 2], 377 (22) [M⁺ - 3], 375 (2) [M⁺ - 5]. Anal. Calcd for C₁₆H₁₉N₃O₃Se: C, 50.53; H, 5.04; N, 11.05. Found: C, 50.48; H, 5.21; N, 10.96.

<A NAME="RD39109ST-15">15</A> Attanasi OA. De Crescentini L. Filippone P. Foresti E. Mantellini F. J. Org. Chem. 2000, 65: 2820

General Procedure for the Synthesis of α-(Phenylseleno)-hydrazones 6a-c and α-(1,3-Benzoselenazol-2-ylthio)-hydrazones 6d-f A solution of 1,2-diaza-1,3-butadienes 1a-c as a mixture of E/Z isomers [¹8] (1.0 mmol) and phenylselenol(2c) or 2-mercaptobenzselenazole (2d, 1.0 mmol) in THF (5 mL) was magnetically stirred at r.t., for 0.1-24.0 h until the disappearance of the starting 1. Ηydrazones 6a-c were obtained by chromatography on SiO₂ column (elution mixtures: cyclohexane-EtOAc) and by subsequent crystallization from Et₂O-light PE (40-60), while hydrazones 6d-f were crystallized from Et₂O-light PE
(40-60), after the evaporation of the reaction solvent. The conversion of α-(1,3-benzoselenazol-2-ylthio)hydrazones 6d-f into the corresponding hydrazino forms occurred in one week, directly in the NMR tube, using DMSO-d ₆ as solvent.
Methyl 3-[(Aminocarbonyl)hydrazono]-2-(phenylseleno)-pentanoate (6b)
Yield 247.5 mg (72%) obtained as white solid; mp 124-126 ˚C. IR (Nujol): ν_max = 3454, 3299, 3191, 1793, 1697 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 0.93 (t, 3 H, J = 7.6 Hz), 2.33-2.38 (m, 2 H), 3.60 (s, 3 H), 4.94 (s, 1 H), 6.18 (br s, 2 H), 7.30-7.32 (m, 3 H), 7.54-7.56 (m, 2 H), 9.44 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆) : δ = 9.6 (q), 21.0 (t), 50.1 (d), 52.5 (q), 128.1 (s), 128.2 (d), 129.1 (d), 134.1 (d), 145.8 (s), 156.8 (s), 169.8 (s). MS: m/z (%) = 345 (8)[M⁺ + 3], 343 (35) [M⁺ + 1], 341 (17) [M⁺ - 1], 340 (6) [M⁺ - 2], 339 (6) [M⁺ - 3], 337 (1) [M⁺ - 5], 317 (3), 315 (15), 313 (9), 312 (4), 311 (4), 270 (6), 268 (30), 266 (15), 265 (6), 264 (6), 262 (2), 186 (100). Anal. Calcd for C₁₃H₁₇N₃O₃Se: C, 45.62; H, 5.01; N, 12.28. Found: C, 45.48; H, 5.17; N, 12.41.
Ethyl 3-[(Aminocarbonyl)hydrazono]-2-(1,3-benzo-selenazol-2-ylthio)butanoate (Hydrazono Form of 6d)
Yield 372.5 mg (93%) obtained as white solid; mp 144-146 ˚C. IR (Nujol): ν_max = 3463, 3313, 3200, 1790, 1692 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.20 (t, 3 H, J = 7.2 Hz), 1.98 (s, 3 H), 4.16-4.24 (m, 2 H), 5.51 (s, 1 H), 6.28 (br s, 2 H), 7.29 (t, 1 H, J = 8.0 Hz), 7.44 (t, 1 H, J = 8.0 Hz), 7.78 (d, 1 H, J = 7.2 Hz), 8.04 (d, 1 H, J = 6.8 Hz), 9.55 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆) : δ = 13.9 (q), 14.5 (q), 57.4 (t), 61.9 (d), 122.5 (d), 124.6 (d), 125.3 (d), 126.4 (d), 138.3 (s), 140.5 (s), 153.6 (s), 156.6 (s), 166.1 (s), 167.5 (s); MS: m/z (%) = 400 (1) [M⁺ + 3], 398 (5) [M⁺ + 1], 396 (2) [M⁺ - 1], 397 (1) [M⁺ - 2], 396 (1) [M⁺ - 3], 328 (9), 326 (45), 324 (19), 323 (8), 322 (8), 320 (1), 313 (31), 311 (100), 309 (60), 308 (24), 307 (23), 305 (3); Anal. Calcd for C₁₄H₁₆N₄O₃SSe: C, 42.11; H, 4.04; N, 14.03. Found: C, 42.31; H, 4.11; N, 14.20.
Ethyl 3-[2-(Aminocarbonyl)hydrazino]-2-(1,3-benzo-selenazol-2-ylthio)but-2-enoate (Hydrazino Form of 6d)
^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.11 (t, 3 H, J = 7.2 Hz), 2.30 (s, 3 H), 4.09 (q, 2 H, J = 7.2 Hz), 6.28 (s, 2 H), 7.21 (t, 1 H, J = 8.0 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.75 (d, 1 H, J = 6.8 Hz), 7.96 (d, 1 H, J = 8.0 Hz), 8.60 (s, 1 H), 11.08 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 14.3 (q), 16.4 (q), 59.9 (t), 82.3 (s), 122.4 (d), 123.7 (d), 125.0 (d), 126.1 (d), 137.8 (s), 156.8 (s), 157.8 (s), 168.7 (s), 172.4 (s), 180.3 (s).

General Procedure for the Synthesis of 4-(Phenylseleno)-pyrazol-3-ones 7a,b, 8a and 4-(1,3-benzoselenazol-2-ylthio)pyrazol-3-ones 7c,d, 8b
α-(Phenylseleno)- or α-(1,3-benzoselenazol-2-ylthio)hydra-zones (6a-c and 6d-f, 1.0 mmol) were dissolved in a mixture of THF (5 mL)-MeOH (5 mL), and a stoichiometric amount of NaH (1.0 mmol) was added. The reaction mixture was magnetically stirred for 0.1-0.3 h until the disappear-ance of the starting 6. Pyrazol-3-ones 7a-d were obtained from 6a,b,d,e, respectively, while pyrazol-3-ones 8a,b were obtained from 6c,f, respectively. Products 7a-d and 8a,b were purified by chromatography on SiO₂ column (elution mixtures: EtOAc-MeOH) and by subsequent crystallization from Et₂O-light PE (40-60).
5-Ethyl-4-(phenylseleno)-1,2-dihydro-3 H -pyrazol-3-one (7b)
Yield 252.1 mg (94%) obtained as white solid; mp 120-122 ˚C. IR (Nujol): ν_max = 3369, 3116, 1735, 1702, 1636 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 1.03 (t, 3 H, J = 7.6 Hz), 2.35-2.41 (m, 2 H), 7.18-7.32 (m, 4 H), 7.46 (br s, 1 H), 7.57-7.59 (m, 1 H), 8.65 (br s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.1 (q), 20.8 (d), 125.2 (s), 127.7 (d), 128.9 (d), 129.5 (d), 130.8 (s), 158.6 (s), 164.4 (s). MS: m/z (%) = 270 (20)[M⁺ + 3], 268 (100) [M⁺ + 1], 266 (39) [M⁺ - 1], 265 (19) [M⁺ - 2], 264 (21) [M⁺ - 3], 262 (2) [M⁺ - 5]. Anal. Calcd for C₁₁H₁₂N₂OSe: C, 49.45; H, 4.53; N, 10.48. Found: C, 49.49; H, 4.47; N, 10.41.

4-(1,3-Benzoselenazol-2-ylthio)-5-methyl-1,2-dihydro-3 H -pyrazol-3-one (7c) Yield 309.1 mg (99%) obtained as white solid; mp 192-194 ˚C. IR (Nujol): ν_max = 3398, 3328, 1739, 1697, 1673, 1655 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.02 (s, 3 H), 7.01 (s, 1 H), 7.15 (t, 1 H, J = 7.6 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 7.69 (d, 1 H, J = 8.0 Hz), 7.86 (d, 1 H, J = 8.0 Hz), 8.39 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.4 (q), 80.7 (s), 122.1 (d), 123.2 (d), 124.9 (d), 125.8 (d), 138.0 (s), 153.1 (s), 157.3 (s), 165.8 (s), 184.2 (s). MS: m/z (%) = 313 (28) [M⁺ + 3], 311 (100) [M⁺ + 1], 309 (52) [M⁺ - 1], 308(18) [M⁺ - 2], 307(18) [M⁺ - 3], 305 (1) [M⁺ - 5]. Anal. Calcd for C₁₁H₉N₃OSSe: C, 42.59; H, 2.92; N, 13.54. Found: C, 42.39; H, 3.01; N, 13.28. 3-Methyl-5-oxo- N -phenyl-4-(phenylseleno)-2,5-dihydro-1 H -pyrazole-1-carboxamide (8a) Yield 292.1 mg (78%) obtained as white solid; mp 144-147 ˚C. IR (Nujol): ν_max = 3342, 3191, 1721, 1687 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.12 (s, 3 H), 6.98 (t, 1 H, J = 7.2 Hz), 7.24-7.28 (m, 5 H), 7.45 (br s, 1 H), 7.51-7.68 (m, 4 H), 11.98 (br s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.0 (q), 110.4 (s), 119.1 (d), 122.1 (d), 127.7 (d), 127.8 (d), 129.0 (d), 129.5 (d), 130.8 (s), 139.1 (s), 147.3 (s), 154.2 (s), 164.8 (s). MS: m/z (%) = 375 (20) [M⁺ + 3], 373 (100) [M⁺ + 1], 371 (41) [M⁺ - 1], 370 (19) [M⁺ - 2], 369 (21) [M⁺ - 3], 367 (3) [M⁺ - 5]. Anal. Calcd for C₁₇H₁₅N₃O₂Se: C, 54.85; H, 4.06; N, 11.29. Found: C, 54.96; H, 4.17; N, 11.36.
4-(1,3-Benzoselenazol-2-ylthio)-3-methyl-5-oxo- N -phenyl-2,5-dihydro-1 H -pyrazol-1-carboxamide (8b)
Yield 417.1 mg (97%) obtained as white solid; mp 246-248 ˚C. IR (Nujol): ν_max = 3351, 3186, 1706, 1683 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.10 (s, 3 H), 7.05 (t, 1 H, J = 7.6 Hz), 7.17 (t, 1 H, J = 7.6 Hz), 7.32-7.51 (m, 4 H), 7.54 (d, 2 H, J = 8.0 Hz), 7.72 (d, 1 H, J = 8.0 Hz), 7.88 (d, 1 H, J = 8.0 Hz), 12.21 (s, 1 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.4 (q), 81.2 (s), 119.0 (d), 122.2 (d), 122.7 (d), 123.4 (d), 124.9 (d), 125.8 (d), 129.0 (d), 138.0 (s), 138.7 (s), 149.6 (s), 152.8 (s), 157.2 (s), 165.8 (s), 183.3 (s). MS: m/z (%) = 430 (14) [M⁺ + 3], 428 (45) [M⁺ + 1], 426 (35) [M⁺ - 1], 425 (12) [M⁺ - 2], 424 (13) [M⁺ - 3], 422 (2) [M⁺ - 5], 313 (15), 311 (55), 309 (26), 308 (10), 307 (10), 305 (2), 215 (100). Anal. Calcd for C₁₈H₁₄N₄O₂SSe: C, 50.35; H, 3.29; N, 13.05. Found: C, 50.39; H, 3.31; N, 13.23.

<A NAME="RD39109ST-18A">18a</A> Attanasi OA. Filippone P. Mei A. Santeusanio S. Synthesis 1984, 671

<A NAME="RD39109ST-18B">18b</A> Attanasi OA. Filippone P. Mei A. Santeusanio S. Synthesis 1984, 873